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Protein

Nucleic acid dioxygenase ALKBH1

Gene

ALKBH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dioxygenase that acts as on nucleic acids, such as DNA and tRNA (PubMed:18603530, PubMed:27745969, PubMed:27497299). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:18603530, PubMed:27497299). A number of activities have been described for this dioxygenase, but recent results suggest that it mainly acts as on tRNAs and mediates their demethylation or oxidation depending on the context and subcellular compartment (PubMed:27745969, PubMed:27497299). Mainly acts as a tRNA demethylase by removing N1-methyladenine from various tRNAs, with a preference for N1-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs (PubMed:27745969). Acts as a regulator of translation initiation and elongation in response to glucose deprivation: regulates both translation initiation, by mediating demethylation of tRNA(Met), and translation elongation, N1-methyladenine-containing tRNAs being preferentially recruited to polysomes to promote translation elongation (PubMed:27745969). In mitochondrion, specifically interacts with mt-tRNA(Met) and mediates oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f5c) at this position (PubMed:27497299). mt-tRNA(Met) containing the f5c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation (PubMed:27497299). Specifically demethylates DNA methylated on the 6th position of adenine (N6-methyladenosine) DNA. N6-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (By similarity). Also able to repair alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation, but with low activity (PubMed:18603530). Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites (PubMed:19959401). DNA lyase activity does not require alpha-ketboglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5' DNA product (PubMed:19959401, PubMed:23577621). DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation. May play a role in placental trophoblast lineage differentiation (By similarity).By similarity5 Publications

Catalytic activityi

The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.1 Publication
DNA-base-CH3 + 2-oxoglutarate + O2 = DNA-base + formaldehyde + succinate + CO2.1 Publication
N6-methyladenine in DNA + 2-oxoglutarate + O2 = adenine in DNA + formaldehyde + succinate + CO2.By similarity
N1-methyladenine in tRNA + 2-oxoglutarate + O2 = adenine in tRNA + formaldehyde + succinate + CO2.1 Publication
5-methylcytosine(34) in mitochondrial tRNA(Met)+ 2-oxoglutarate + O2 = 5-formylcytosine(34) in mitochondrial tRNA(Met) + formaldehyde + succinate + CO2.1 Publication

Cofactori

Fe2+PROSITE-ProRule annotation1 PublicationNote: Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei133Primary catalytic residue forming the imine linkage with DNA1 Publication1
Sitei133Secondary catalytic residue forming the imine linkage with DNA1 Publication1
Binding sitei144SubstrateBy similarity1
Metal bindingi231Iron; catalyticPROSITE-ProRule annotation2 Publications1
Metal bindingi233Iron; catalyticPROSITE-ProRule annotation3 Publications1
Binding sitei233SubstrateBy similarity1
Metal bindingi287Iron; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • developmental growth Source: Ensembl
  • DNA dealkylation involved in DNA repair Source: UniProtKB
  • DNA demethylation Source: UniProtKB
  • DNA repair Source: UniProtKB
  • in utero embryonic development Source: Ensembl
  • negative regulation of neuron apoptotic process Source: Ensembl
  • neuron migration Source: Ensembl
  • neuron projection development Source: Ensembl
  • oxidative demethylation Source: UniProtKB
  • oxidative single-stranded DNA demethylation Source: GO_Central
  • placenta development Source: Ensembl
  • regulation of mitochondrial translation Source: UniProtKB
  • regulation of translational elongation Source: UniProtKB
  • regulation of translational initiation Source: UniProtKB
  • RNA repair Source: UniProtKB
  • tRNA demethylation Source: UniProtKB
  • tRNA wobble cytosine modification Source: UniProtKB

Keywordsi

Molecular functionDioxygenase, Lyase, Oxidoreductase
Biological processDNA damage, DNA repair, RNA repair, Translation regulation
LigandIron, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleic acid dioxygenase ALKBH1Curated (EC:1.14.11.-1 Publication)
Alternative name(s):
Alkylated DNA repair protein alkB homolog 11 Publication
Alpha-ketoglutarate-dependent dioxygenase ABH11 Publication
DNA 6mA demethylaseBy similarity
DNA N6-methyl adenine demethylaseBy similarity (EC:1.14.11.-By similarity)
DNA lyase ABH11 Publication (EC:4.2.99.181 Publication)
DNA oxidative demethylase ALKBH1 (EC:1.14.11.331 Publication)
tRNA N1-methyl adenine demethylase1 Publication (EC:1.14.11.-1 Publication)
Gene namesi
Name:ALKBH1Imported
Synonyms:ABH1 Publication, ABH11 Publication, ALKBH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100601.9.
HGNCiHGNC:17911. ALKBH1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi25K → A: Moderate decrease in DNA lyase activity. Reduced DNA lyase activity; when associated with A-133. 1 Publication1
Mutagenesisi55K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi61K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi64K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi87K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi94K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi113H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi116K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi118C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi120K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi125K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi129C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi133K → A: Reduced DNA lyase activity. Slightly more reduced DNA lyase activity; when associated with A-25. Strongly reduced activity; when associated with A-154. 1 Publication1
Mutagenesisi134H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi137K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi148K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi154K → A: Does not affect DNA lyase activity. Strongly reduced activity; when associated with A-133. 1 Publication1
Mutagenesisi158K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi167K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi182K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi183K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi218I → L: Reduces Fe2OG dioxygenase activity by 50%. 1 Publication1
Mutagenesisi231 – 233HVD → AVA: Loss of catalytic activity. Abolishes ability to regulate translation in respose to glucose deprivation. 1 Publication3
Mutagenesisi231H → A: Near loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. 2 Publications1
Mutagenesisi233D → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Abolishes ability to mediate oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f(5)c). 3 Publications1
Mutagenesisi241K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi287H → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. 2 Publications1
Mutagenesisi303H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi304C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi335K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi338R → A: Reduced Fe2OG dioxygenase activity. Abolishes ability to mediate oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f(5)c). 2 Publications1
Mutagenesisi344R → A: Reduced Fe2OG dioxygenase activity. 1 Publication1
Mutagenesisi362K → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi371C → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi372H → A: Does not affect DNA lyase activity. 1 Publication1
Mutagenesisi381K → A: Does not affect DNA lyase activity. 1 Publication1

Organism-specific databases

DisGeNETi8846.
OpenTargetsiENSG00000100601.
PharmGKBiPA134906996.

Polymorphism and mutation databases

BioMutaiALKBH1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000666681 – 389Nucleic acid dioxygenase ALKBH1Add BLAST389

Proteomic databases

EPDiQ13686.
MaxQBiQ13686.
PaxDbiQ13686.
PeptideAtlasiQ13686.
PRIDEiQ13686.

PTM databases

iPTMnetiQ13686.
PhosphoSitePlusiQ13686.

Expressioni

Tissue specificityi

Ubiquitous.2 Publications

Gene expression databases

BgeeiENSG00000100601.
CleanExiHS_ALKBH1.
ExpressionAtlasiQ13686. baseline and differential.
GenevisibleiQ13686. HS.

Organism-specific databases

HPAiHPA044087.

Interactioni

Subunit structurei

Monomer (PubMed:19959401). Interacts with DNAJB6 (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi114372. 2 interactors.
IntActiQ13686. 1 interactor.
STRINGi9606.ENSP00000216489.

Structurei

3D structure databases

ProteinModelPortaliQ13686.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini208 – 347Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST140

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni86 – 389tRNA-binding1 PublicationAdd BLAST304
Regioni175 – 177Substrate bindingBy similarity3
Regioni220 – 222Alpha-ketoglutarate bindingBy similarity3
Regioni338 – 344Alpha-ketoglutarate bindingBy similarity7

Sequence similaritiesi

Belongs to the alkB family.Curated

Phylogenomic databases

eggNOGiKOG2731. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00390000004599.
HOGENOMiHOG000033905.
HOVERGENiHBG050487.
InParanoidiQ13686.
KOiK10765.
OMAiCYHAVPR.
OrthoDBiEOG091G0A10.
PhylomeDBiQ13686.
TreeFamiTF314609.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
InterProiView protein in InterPro
IPR004574. Alkb.
IPR027450. AlkB-like.
IPR037151. AlkB-like_sf.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
PANTHERiPTHR16557. PTHR16557. 1 hit.
PfamiView protein in Pfam
PF13532. 2OG-FeII_Oxy_2. 1 hit.
TIGRFAMsiTIGR00568. alkb. 1 hit.
PROSITEiView protein in PROSITE
PS51471. FE2OG_OXY. 1 hit.

Sequencei

Sequence statusi: Complete.

Q13686-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKMAAAVGS VATLATEPGE DAFRKLFRFY RQSRPGTADL EGVIDFSAAH
60 70 80 90 100
AARGKGPGAQ KVIKSQLNVS SVSEQNAYRA GLQPVSKWQA YGLKGYPGFI
110 120 130 140 150
FIPNPFLPGY QWHWVKQCLK LYSQKPNVCN LDKHMSKEET QDLWEQSKEF
160 170 180 190 200
LRYKEATKRR PRSLLEKLRW VTVGYHYNWD SKKYSADHYT PFPSDLGFLS
210 220 230 240 250
EQVAAACGFE DFRAEAGILN YYRLDSTLGI HVDRSELDHS KPLLSFSFGQ
260 270 280 290 300
SAIFLLGGLQ RDEAPTAMFM HSGDIMIMSG FSRLLNHAVP RVLPNPEGEG
310 320 330 340 350
LPHCLEAPLP AVLPRDSMVE PCSMEDWQVC ASYLKTARVN MTVRQVLATD
360 370 380
QNFPLEPIED EKRDISTEGF CHLDDQNSEV KRARINPDS
Length:389
Mass (Da):43,832
Last modified:December 1, 2000 - v2
Checksum:i539C4CE41D2D8AEC
GO

Sequence cautioni

Q13686: The sequence CAA63047 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133K → T in CAA63047 (PubMed:8600462).Curated1
Sequence conflicti266 – 267TA → PP in CAA63047 (PubMed:8600462).Curated2
Sequence conflicti388D → H in AAH25787 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048221135M → I. Corresponds to variant dbSNP:rs17825440Ensembl.1
Natural variantiVAR_048222324M → L. Corresponds to variant dbSNP:rs6494Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91992 mRNA. Translation: CAA63047.1. Frameshift.
AC008044 Genomic DNA. Translation: AAF01478.1.
BC025787 mRNA. Translation: AAH25787.1.
CCDSiCCDS32127.1.
PIRiS64736.
RefSeqiNP_006011.2. NM_006020.2.
UniGeneiHs.94542.

Genome annotation databases

EnsembliENST00000216489; ENSP00000216489; ENSG00000100601.
GeneIDi8846.
KEGGihsa:8846.
UCSCiuc001xuc.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiALKB1_HUMAN
AccessioniPrimary (citable) accession number: Q13686
Secondary accession number(s): Q8TAU1, Q9ULA7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: October 25, 2017
This is version 143 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

The DNA N6-methyl adenine demethylase activity is unclear in vivo. According to a recent report, biochemical assays do not reveal clear DNA N6-methyl adenine demethylase activity in vivo.1 Publication

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families